This application pertains to compositions for tailored drug delivery of a pharmaceutical agent to a specific cell, tissue, or organ type using naturally occurring affinities.
Many drug candidates fail to advance through the drug-development pipeline because of harmful side-effects. Often these problems are associated with the use of passive drug delivery, which relies on the absorption of a drug across the biological membrane of all cells. When systemically administered by passive drug delivery to a patient, many drugs will only reach the targeted cells in low concentrations, with the remaining drug either non-specifically collecting in other parts of the body (e.g. high concentrations in the liver and plasma) or being cleared from the body. This is of particular concern for drugs having a high cytotoxic potential, such as chemotherapy agents, which can damage healthy as well as diseased cells. A targeted delivery of pharmaceutical agents is highly desirable because via this mechanism accurate dosages of an effective drug may be delivered selectively to diseased cells and would either totally avoid or reduce the amount of drug exposure to normal, healthy cells and tissues.
Different types of drug delivery vehicles have been explored such as, polymeric micelles, polymeric nanovehicle, liposomes, polymersomes, nanospheres, nanocapsules, dendrimers, proteins, cell ghosts, inorganic/metallic and bacterial delivery vehicles (Alexis et al. 2010; Matsumura and Kataoka 2009; Wang et al. 2009). Many of these approaches require the use of large proteins which may be expensive to produce. Additionally, many of the currently employed drug delivery vehicles fail to address the problem of simultaneously impacting healthy cells and tissues via the drug employed.
Ideally, a targeted drug delivery vehicle should act specifically on the diseased cell of interest, while avoiding toxic side-effects on healthy cells. Furthermore, the delivery agent should be largely non-immunogenic, have extended residence time in the blood and be biodegradable. Furthermore, the system as whole should be amenable to address a broad range of diseases and be amenable to scale up and manufacturing at a commercial-scale level.
The current invention provides drug delivery compositions, methods of manufacture and methods of treatment for therapeutic applications that can overcome several challenges currently presented in pharmaceutical development.